| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy of LY3009104 as assessed by the aggregate proportion of patients in the 4 mg and 8 mg dose groups who achieve an ACR20 response compared to placebo over 12 weeks in patients with active RA despite ongoing MTX
therapy. |
|
| E.2.2 | Secondary objectives of the trial |
1 - To characterize the dose-response relationship of LY3009104 on ACR (20/50/N)
response rates over 12 weeks and to evaluate model-predicted responses for each dose versus placebo to identify one or more efficacious doses.
2 - To evaluate the efficacy of each dose of LY3009104 compared to placebo over 12 weeks.
3 - To evaluate the relative efficacy of each dose of LY3009104 over 24 weeks.
4 - To evaluate the safety and tolerability of LY3009104 compared to placebo.
5 - To evaluate the efficacy of twice-daily dosing of 2 mg of LY3009104 as compared to once-daily dosing of 4 mg of LY3009104.
6 - To evaluate the safety of twice-daily dosing of 2 mg of LY3009104 as compared to once daily dosing of 4 mg of LY3009104 as assessed by standard safety measures.
7 - To characterize the pharmacokinetics of LY3009104 and explore dose/PK relationships.
8 - To evaluate the impact of LY3009104 compared to placebo over the 12-week study period with regard to patient-reported outcomes. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Addendum I4V-MC-JADA(1), dated 11 August 2010.
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients with Active Rheumatoid Arthritis on Background Methotrexate Therapy |
|
| E.3 | Principal inclusion criteria |
[1] Ambulatory males or females between the ages of 18 and 75 years, inclusive.
[1a] Male patients: Agree to use a reliable method of birth control during the study.
[1b] Female patients: Females must not be pregnant, breastfeeding, or at risk to become pregnant during study participation. Female patients of childbearing potential, must test negative for pregnancy at the time of enrollment and agree to use a reliable method of birth control or remain abstinent during the study or for at
least 30 days following the last dose of study drug, whichever is longer, or,
must be a female of non-childbearing potential, defined as:
- women who have had surgical sterilization (hysterectomy or bilateral
oophorectomy or tubal ligation),
- women ≥60 years of age, or
- women ≥40 and <60 years of age who have had a cessation of menses for
at least 12 months and a follicle-stimulating hormone (FSH) test
confirming non-childbearing potential (FSH ≥40 mIU/mL).
[2] Diagnosis of adult-onset RA (of at least 6 months duration but not longer than
15 years prior to screening) according to the ARA 1987 Revised Criteria for
the Classification of RA (Arnett et al. 1988).
[3] Have active RA defined as at least 8 swollen and at least 8 tender joints based
on the 66/68 joint count (Smolen et al. 1995).
[4] Regular use of MTX for at least 12 weeks, and treatment at a stable dose of
10 to 25 mg/week for at least 8 weeks prior to baseline. The dose of MTX
should remain stable throughout the study, but may be adjusted for safety
reasons. Local standard of care should be followed for concomitant
administration of folic acid.
[5] For patients receiving corticosteroids, they must be on a dose not to exceed
10 mg of prednisone daily (or equivalent) and have been on a stable dose for
at least 6 weeks prior to randomization.
[6] ACR functional class I, II, or III (Hochberg et al. 1992).
[7] Have C-reactive protein (CRP) measurement > 1.2 times upper limit of
normal (ULN) or Erythrocyte Sedimentation Rate (ESR) > upper limit of
normal (28 mm/hr). The CRP and ESR may be repeated once during the
screening period at the discretion of the investigator, and the repeat results
may be accepted for study eligibility purposes.
[8] Clinical laboratory test results within normal reference range for the central
laboratory. (Note: This inclusion criterion only applies to clinical laboratory
tests not specifically cited in any exclusion criteria below.)
[9] Venous access sufficient to allow blood sampling as per the protocol.
[10] Are reliable and willing to be available for the duration of the study and are
willing to follow study procedures.
[11] Are able to read, understand, and give written informed consent approved by
Lilly or its designee and the ethical review board (ERB) governing the site. |
|
| E.4 | Principal exclusion criteria |
[1] Have received any parenteral corticosteroid administered by intra-articular,
intramuscular, or IV injection within 6 weeks prior to baseline.
[2] Have received either oral corticosteroids at average daily doses of >10 mg/day
of prednisone (or equivalent) or used variable doses of oral corticosteroids
within 6 weeks prior to baseline.
[3] Use of NSAIDs for less than 4 weeks prior to baseline.
[4] Have received any prior biologic DMARD therapy (such as TNFα, IL-1, IL-6,
T-cell or B-cell targeted therapies).
[5] Have previously completed or withdrawn from this study or any other study
investigating LY3009104.
[6] Received prior treatment with an oral JAK inhibitor.
[7] Use of DMARDs other than stable treatment of MTX,
hydroxychloroquine (up to 400 mg/day), and/or sulfasalazine (up to
3000 mg/day) in the 8 weeks prior to baseline.
[8] Use of leflunomide in the 12 weeks prior to baseline (or a minimum of
4 weeks prior to baseline will be required if the standard 11 days of
chlolestyramine is used to washout leflunomide).
[9] Have active fibromyalgia that would make it difficult to appropriately assess
RA activity for the purposes of this study or have a diagnosis of any systemic
inflammatory condition other than RA. Patients with secondary Sjogren's syndrome with RA are not excluded.
[10] Have evidence of active vasculitis.
[11] Have a diagnosis of Felty’s syndrome.
[12] Had surgical treatment of a joint that is to be assessed in the study within
2 months of study baseline or will require such during the study.
[13] An abnormality in the 12-lead ECG that in the opinion of the investigator
increases the risk of participating in the study.
[14] Uncontrolled arterial hypertension characterized by a systolic BP >160 mmHg
or diastolic BP >100 mmHg.
[15] Have had lymphoma, leukemia, or any malignancy within the past 5 years,
except for cervical carcinoma in situ that has been resected with no evidence
of recurrence or metastatic disease, or basal cell or squamous epithelial skin
cancers that have been completely resected with no evidence of recurrence for
at least 3 years.
[16] History or presence of cardiovascular, respiratory, hepatic, renal,
gastrointestinal, endocrine, hematological, or neurological disorders that in the
opinion of the investigator could constitute a risk or of interfere with the interpretation of data.
[17] Evidence of significant active neuropsychiatric disease, in the opinion of the
investigator.
[18] Have a current or recent (<30 days prior to screening) viral, bacterial, fungal,
or parasitic infection.
[19] Had a serious infection or atypical mycobacterial infection within 6 months prior to screening.
[20] Had symptomatic herpes zoster or herpes simplex infection within 90 days
prior to baseline.
[21] History of disseminated/complicated herpes zoster.
[22] Evidence of human immunodeficiency virus (HIV) infection and/or positive
human HIV antibodies.
[23] Have evidence of active or test positive for hepatitis C virus (HCV).
[24] Evidence of active hepatitis B (positive for hepatitis B surface antigen
[HBsAg+]) OR are positive for hepatitis B core antibody and negative for
hepatitis B surface antibody (HBcAb+, HBsAb-).
[25] Evidence of active or latent tuberculosis (TB) as documented by a positive
purified protein derivative (PPD) test (≥5 mm in duration between
approximately 2 and 3 days after application.
[26] Exposed to a live vaccine within 12 weeks prior to baseline or expected to
need/receive a live vaccine (includes Herpes zoster vaccination) during the
course of the study.
[27] Have any significant hematological abnormalities listed below:
o Hemoglobin less than 10.0 g/dL,
o Total platelet count less than 100,000/μL ,
o Total white blood cell (WBC) count less than 2500/μL,
o Neutrophil count equal to or less than 1200/μL
o Lymphocyte count equal to or less than 750 cells/μL.
[28] Have estimated glomerular filtration rate (GFR) from serum creatinine using
the Modification of Diet in Renal Disease (MDRD) method of < 50mL/minute.
[29] Have known history hypogammaglobulinemia.
[30] Have any history of chronic liver disease or current serum aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) concentration >3x
the ULN or total bilirubin is ≥1.5x ULN.
[31] Blood donation of more than 500 mL within 30 days prior to screening.
[32] Are investigator site personnel directly affiliated with this study and/or their
immediate families.
[33] Are Lilly or Incyte employees or either’s designee.
[34] Are currently enrolled in, or discontinued within the last 30 days from a
clinical study involving an investigational drug or device or off-label use of a
drug (other than the study drug used in this study), or concurrently enrolled in
any other type of medical research judged not to be scientifically or medically
compatible with this study.
[35] Women who are lactating or breast feeding. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary analysis will be a comparison of the combined 4 mg and 8 mg dose groups with placebo on the ACR20 response rate at 12 weeks. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
